Mechanisms underlying direction selectivity of neurons in the primary visual cortex of the macaque

1. We studied the effects of blocking intracortical inhibition by microiontophoretic administration of bicuculline methiodide (BMI), a selective antagonist for gamma-aminobutyric acid-A receptors, on direction sensitivity of 103 neurons in the primary visual cortex (VI) of anesthetized and paralyzed monkeys. 2. The direction selectivity index (DSI) of each cell was calculated for the control response and response during the BMI administration at the optimal stimulus orientation to assess the directionality of an individual cell. 3. The averaged direction tuning of visual responses of cells was sharp in layers IVa and IVb, moderate in both interblob and blob regions of layer II/III and layers V and VI, and poor in layers IVc alpha and IVc beta. 4. Iontophoretic administration of BMI uncovered or facilitated responses to stimuli moving in the nonpreferred direction, and reduced DSIs of cells to a varying extent in all the layers except layer VI. Responses to stimuli moving in the preferred direction were also facilitated so that a slight bias of response toward the originally preferred direction remained during BMI administration in most cells. 5. Most of the cells in layers II/III (both blobs and interblobs) and IVb that receive inputs from layers IVc alpha and IVc beta showed a clear reduction of direction selectivity during BMI administration. This result suggests that intracortical inhibition plays an important role in the elaboration of direction selectivity at the second stage of information processing in VI. 6. The direction selectivity of cells in layer VI was most resistant to the effects of BMI, suggesting that it is dependent on excitatory inputs that are already direction selective, even though the sample size of this layer was small. 7. In direction-selective cells outside layer VI, responses to a stimulus moving in the preferred direction were enhanced in a way that was linearly related with those in the nonpreferred direction as the BMI dose was increased. This suggests that various amounts of inhibition interact linearly with directionally biased excitatory inputs to raise the firing threshold to various levels so as to produce various degrees of directionality. 8. These results suggest that, in most of the directionally sensitive cells except for those in layer VI, there are excitatory inputs which are bidirectional but slightly biased to one direction, and that the intracortical inhibition raises a threshold level of responses to excitatory inputs so that the response become direction selective.     

Mechanisms of direction selectivity in macaque V1

Mechanisms underlying direction selectivity were studied in V1 of alert fixating macaque monkeys. Some direction-selective cells showed delayed asymmetric inhibition, some showed a shifting excitatory time course across the receptive field, and some showed both. Both the direction of the spatial offset of the inhibition and the direction of the shift in excitatory response time course correlated with the cells' preferred directionality. The delayed asymmetric inhibition may contribute to the shifting response time course. The data suggest that asymmetric inhibition is the major determinant for directionality in these cells, though both mechanisms could contribute. Based on this physiology, a simple, single-cell model is proposed, consistent with the known anatomy of some direction-selective cells.     

Linearity of summation of synaptic potentials underlying direction selectivity in simple cells of the cat visual cortex

Intracellular recordings from simple cells of the cat visual cortex were used to test linear models for the generation of selectivity for the direction of visual motion. Direction selectivity has been thought to arise in part from nonlinear processes, as suggested by previous experiments that were based on extracellular recordings of action potentials. In intracellular recordings, however, the fluctuations in membrane potential evoked by moving stimuli were accurately predicted by the linear summation of responses to stationary stimuli. Nonlinear mechanisms were not required.     

Linearity and normalization in simple cells of the macaque primary visual cortex

Simple cells in the primary visual cortex often appear to compute a weighted sum of the light intensity distribution of the visual stimuli that fall on their receptive fields. A linear model of these cells has the advantage of simplicity and captures a number of basic aspects of cell function. It, however, fails to account for important response nonlinearities, such as the decrease in response gain and latency observed at high contrasts and the effects of masking by stimuli that fail to elicit responses when presented alone. To account for these nonlinearities we have proposed a normalization model, which extends the linear model to include mutual shunting inhibition among a large number of cortical cells. Shunting inhibition is divisive, and its effect in the model is to normalize the linear responses by a measure of stimulus energy. To test this model we performed extracellular recordings of simple cells in the primary visual cortex of anesthetized macaques. We presented large stimulus sets consisting of (1) drifting gratings of various orientations and spatiotemporal frequencies; (2) plaids composed of two drifting gratings; and (3) gratings masked by full-screen spatiotemporal white noise. We derived expressions for the model predictions and fitted them to the physiological data. Our results support the normalization model, which accounts for both the linear and the nonlinear properties of the cells. An alternative model, in which the linear responses are subject to a compressive nonlinearity, did not perform nearly as well.     

Temporal dynamics of chromatic tuning in macaque primary visual cortex

The ability to distinguish colour from intensity variations is a difficult computational problem for the visual system because each of the three cone photoreceptor types absorb all wavelengths of light, although their peak sensitivities are at relatively short (S cones), medium (M cones), or long (L cones) wavelengths. The first stage in colour processing is the comparison of the outputs of different cone types by spectrally opponent neurons in the retina and upstream in the lateral geniculate nucleus. Some neurons receive opponent inputs from L and M cones, whereas others receive input from S cones opposed by combined signals from L and M cones. Here we report how the outputs of the L/M- and S-opponent geniculate cell types are combined in time at the next stage of colour processing, in the macaque primary visual cortex (V1). Some V1 neurons respond to a single chromatic region, with either a short (68-95 ms) or a longer (96-135 ms) latency, whereas others respond to two chromatic regions with a difference in latency of 20-30 ms. Across all types, short latency responses are mostly evoked by L/M-opponent inputs whereas longer latency responses are evoked mostly by S-opponent inputs. Furthermore, neurons with late S-cone inputs exhibit dynamic changes in the sharpness of their chromatic tuning over time. We propose that the sparse, S-opponent signal in the lateral geniculate nucleus is amplified in area V1, possibly through recurrent excitatory networks. This results in a delayed, sluggish cortical S-cone signal which is then integrated with L/M-opponent signals to rotate the lateral geniculate nucleus chromatic axes.     

GABA-induced inactivation of functionally characterized sites in cat visual cortex (area 18): effects on direction selectivity

1. Microiontophoresis of gamma-aminobutyric acid was used to reversibly inactivate small sites of defined orientation and direction specificity at a horizontal distance of 400-700 microns from single cells recorded in cat area 18. There was extensive or complete overlap between the receptive fields of cells at the recording and inactivation sites. A cell's directionality index [DI: 1 - (response to nonpreferred direction/response to preferred direction)], the response to the preferred direction, and orientation tuning width (measured at half the maximum response) were compared before and during inactivation of either iso-orientation sites (where the orientation preference was within 22.5 degrees) or cross-orientation sites (where it differed by 45-90 degrees). 2. During iso-orientation inactivation, 40 (73%) of 55 cells showed a significant (> 0.20) change in DI; the mean change in DI for these cells was 0.59. An additional cell showed a marked increase in response to the preferred direction that did not result in a change in DI. With one exception, the effects occurred in the absence of a significant (> 25%) change in orientation tuning width. 3. In most cases, the results were broadly predictable in the sense that iso-orientation inactivation predominantly affected a cell's response to the direction of motion of an optimally oriented bar that was closest to the preferred direction at the inactivation site: viz., a decrease in response to the preferred direction and an increase in response to the preferred or nonpreferred direction. 4. It is argued that the decreases in response were due to a reduction in the strength of intracortical iso-orientation excitatory connections made primarily between cells with similar direction preferences, whereas the increases in response involved a loss of iso-orientation inhibition. 5. In cases where remote inactivation caused an increase in response to the nonpreferred direction, comparable effects could be elicited when a mask left exposed only the excitatory subregion of the receptive field in S cells or the most responsive part of the excitatory discharge region in C cells. This implies extensive or complete spatial overlap between the profiles of excitation and inhibition in a cell's nonpreferred direction. 6. During cross-orientation inactivation, a significant change in DI was seen in only 14 (19%) of 73 cells and, with one exception, these changes were accompanied by increases in response to non-optimal orientations and significant broadening of orientation tuning. The effects of cross-orientation inactivation on directionality were presumably due to the loss of cross-orientation inhibition, which contributes primarily to orientation tuning. 7. Inactivation of the same site could cause an increase in response to the nonpreferred direction in cells recorded at iso-orientation sites and an increase in response to nonoptimal orientations and broadening of orientation tuning in cells recorded at cross-orientation sites. This is consistent with the notion that a single inhibitory neuron can contribute to the directionality or orientation tuning of different target cells depending on their location in the orientation map. 8. The results provide evidence for a major contribution of intrinsic mechanisms to the orientation tuning and direction selectivity of cells in cat area 18. It is proposed that two different intracortical processes are involved in the enhancement of orientation and direction selectivity: 1) suppression of responses to nonoptimal orientations and directions as a result of cross-orientation inhibition and iso-orientation inhibition; and 2) facilitation of responses to optimal orientations/directions via iso-orientation excitatory connections.     

Recovery of orientation selectivity in kitten primary visual cortex is slowed down by bilateral section of ophthalmic trigeminal afferents

The recovery of orientation selectivity in the primary visual cortex has been studied in 6-week-old dark-reared (DR) kittens after visual exposure of various durations following bilateral section of either the ophthalmic (V1) or the maxillary (V2) branches of the Vth nerve. After 6 h of vision, visual cortical neurones become orientation selective in V2-operated kittens as well as in intact animals, while they remain non-specific in V1-operated kittens. However, in this latter case, if the duration of visual exposure is extended to 4 weeks, a slow and incomplete recovery of orientation selectivity takes place.     

Representation of spatial frequency and orientation in the visual cortex

Knowledge of the response of the primary visual cortex to the various spatial frequencies and orientations in the visual scene should help us understand the principles by which the brain recognizes patterns. Current information about the cortical layout of spatial frequency response is still incomplete because of difficulties in recording and interpreting adequate data. Here, we report results from a study of the cat primary visual cortex in which we employed a new image-analysis method that allows improved separation of signal from noise and that we used to examine the neurooptical response of the primary visual cortex to drifting sine gratings over a range of orientations and spatial frequencies. We found that (i) the optical responses to all orientations and spatial frequencies were well approximated by weighted sums of only two pairs of basis pictures, one pair for orientation and a different pair for spatial frequency; (ii) the weightings of the two pictures in each pair were approximately in quadrature (1/4 cycle apart); and (iii) our spatial frequency data revealed a cortical map that continuously assigns different optimal spatial frequency responses to different cortical locations over the entire spatial frequency range.     

Object-based attention in the primary visual cortex of the macaque monkey

Typical natural visual scenes contain many objects, which need to be segregated from each other and from the background. Present theories subdivide the processes responsible for this segregation into a pre-attentive and attentive system. The pre-attentive system segregates image regions that 'pop out' rapidly and in parallel across the visual field. In the primary visual cortex, responses to pre-attentively selected image regions are enhanced. When objects do not segregate automatically from the rest of the image, the time-consuming attentive system is recruited. Here we investigate whether attentive selection is also associated with a modulation of firing rates in area V1 of the brain in monkeys trained to perform a curve-tracing task. Neuronal responses to the various segments of a target curve were simultaneously enhanced relative to responses evoked by a distractor curve, even if the two curves crossed each other. This indicates that object-based attention is associated with a response enhancement at the earliest level of the visual cortical processing hierarchy.     

GABAergic inhibitory control of the transient and sustained components of orientation selectivity in a model microcolumn in layer 4 of cat visual cortex

Recently proposed models of orientation tuning in layer 4 of cat primary visual cortex (Somers, Nelson, & Sur, 1995; Douglas, Koch, Mahowald, Martin, & Suarez, 1995) rely on widespread inhibitory intracortical connections to suppress the nonoptimal component of a broadly tuned thalamic input, while local excitatory intracortical connections amplify the optimal component. However, new experimental data (Ferster, Chung, & Wheat, 1996) and theoretical analyses (Ferster, 1987; Krukowski, Priebe, & Miller, 1996) show that the temporally modulated component of thalamic input is well tuned and that the cortical circuitry must simply subtract an unmodulated DC component at nonoptimal orientations to obtain sharp tuning. In addition, within a single hypercolumn in layer 4, inhibitory and excitatory layer 4 neurons have approximately equal-sized axonal fields, making the most of their synapses within their own dendritic field (Kisvarday, Martin, Whitteridge, & Somogyi, 1985; Martin & Whitteridge, 1984). We have constructed a model of a single microcolumn in which GABA inhibition subtracts the DC and controls the sustained response, while GABA inhibition controls the response to transient and suprathreshold inputs. The model fits experimental data based on stimulation with drifting sine-wave gratings as well as flashed bars, explains a counterintuitive property of the GABA conductance, and at suboptimal orientations and submaximal contrasts produces an exponential distribution of firing frequencies.     

Gating of neuronal responses in macaque primary visual cortex by an attentional spotlight

Neuronal responses were recorded from the striate cortex of monkeys trained to perform visual discrimination at locations in the visual field to which their attention was drawn. A subset of neurons showed vigorous responses to visual stimuli for trials in which the monkey was directing its attention to the respective receptive field location. In trials where attention is directed elsewhere, responses to the same stimuli were significantly reduced. In some cells the early response component was not modulated by attention, but later components were affected by the locus of attention. The results suggest the operation of a feedback in the paradigm that spotlights a topographically restricted area of V1 for further processing at higher levels.     

Cortical hierarchy reflected in the organization of intrinsic connections in macaque monkey visual cortex

Neuronal response properties vary markedly at increasing levels of the cortical hierarchy. At present it is unclear how these variations are reflected in the organization of the intrinsic cortical circuitry. Here we analyze patterns of intrinsic horizontal connections at different hierarchical levels in the visual cortex of the macaque monkey. The connections were studied in tangential sections of flattened cortices, which were injected with the anterograde tracer biocytin. We directly compared the organization of connections in four cortical areas representing four different levels in the cortical hierarchy. The areas were visual areas 1, 2, 4 and Brodman's area 7a (V1, V2, V4 and 7a, respectively). In all areas studied, injections labeled numerous horizontally coursing axons that formed dense halos around the injection sites. Further away, the fibers tended to form separate clusters. Many fibers could be traced along the way from the injection sites to the target clusters. At progressively higher order areas, there was a striking increase in the spread of intrinsic connections: from a measured distance of 2.1 mm in area V1 to 9.0 mm in area 7a. Average interpatch distance also increased from 0.61 mm in area V1 to 1.56 mm in area 7a. In contrast, patch size changed far less at higher order areas, from an average width of 230 micron(s) in area V1 to 310 micron(s) in area 7a. Analysis of synaptic bouton distribution along axons revealed that average interbouton distance remained constant at 6.4 micron(s) (median) in and out of the clusters and in the different cortical areas. Larger injections resulted in a marked increase in the number of labeled patches but only a minor increase in the spread of connections or in patch size. Thus, in line with the more global computational roles proposed for the higher order visual areas, the spread of intrinsic connections is increased with the hierarchy level. On the other hand, the clustered organization of the connections is preserved at higher order areas. These clusters may reflect the existence of cortical modules having blob-like dimensions throughout macaque monkey visual cortex.     

Processing of contrast polarity of visual images in inferotemporal cortex of the macaque monkey

Cells in the anterior part of the inferotemporal cortex (anterior IT) respond to moderately complex stimulus features of object images. To study dependency of their responses on contrast polarity of stimulus images, we selected cells with optimal stimuli that were defined only by shape and not related to texture or color, and examined effects of reversing the contrast of the image or removing it except for edges between dark and bright parts of the image ("outlining"). The contrast reversal produced a reduction of the response to the optimal stimulus by > 50% in 60% of tested cells; the outlining, in 70%. When the two transformations were considered together, 94% of the cells showed a reduction by > 50%. Effects of the transformations on shape selectivity were also studied by comparing responses to several different shapes each of whose contours were expressed in different ways. Statistically significant changes in relative effectiveness of the different shapes as a function of contour expression were observed in more than half of the cells. These results suggest that responses of individual cells in anterior IT carry information about contrast polarity as well as about shape.     

Relationships between local synaptic connections and orientation domains in primary visual cortex

Combined optical imaging of ferret primary visual cortex in vivo and scanning laser photostimulation in brain slices were used to determine the spatial relationships between synaptic inputs onto individual neurons and the pattern of orientation columns. In the upper cortical layers, both excitatory and inhibitory inputs originated primarily from regions with orientation tuning similar to that of the recorded neurons; the shapes of the input tuning curves were indistinguishable. The orientation distributions of both types of inputs centered around the orientation of the recorded neurons, and no evidence for preferential cross-orientation inputs, either excitatory or inhibitory, was observed. These patterns of synaptic connectivity are most consistent with feedforward models for generation of orientation selectivity and are inconsistent with the patterns required by models based on cross-orientation inhibition.     

Inputs to directionally selective simple cells in macaque striate cortex

It is clear that the initial analysis of visual motion takes place in the striate cortex, where directionally selective cells are found that respond to local motion in one direction but not in the opposite direction. Widely accepted motion models postulate as inputs to directional units two or more cells whose spatio-temporal receptive fields (RFs) are approximately 90 degrees out of phase (quadrature) in space and in time. Simple cells in macaque striate cortex differ in their spatial phases, but evidence is lacking for the varying time delays required for two inputs to be in temporal quadrature. We examined the space-time RF structure of cells in macaque striate cortex and found two subpopulations of (nondirectional) simple cells, some that show strongly biphasic temporal responses, and others that are weakly biphasic if at all. The temporal impulse responses of these two classes of cells are very close to 90 degrees apart, with the strongly biphasic cells having a shorter latency than the weakly biphasic cells. A principal component analysis of the spatio-temporal RFs of directionally selective simple cells shows that their RFs could be produced by a linear combination of two components; these two components correspond closely in their respective latencies and biphasic characters to those of strongly biphasic and weakly biphasic nondirectional simple cells, respectively. This finding suggests that the motion system might acquire the requisite temporal quadrature by combining inputs from these two classes of nondirectional cells (or from their respective lateral geniculate inputs, which appear to be from magno and parvo lateral geniculate cells, respectively).     

Clustering of response selectivity in the medial superior temporal area of extrastriate cortex in the macaque monkey

The evolution of the medical responsibility cannot escape from the determining influence of the scientific progress, but it is also significantly influenced by sociological and psychological factors that often are more difficult to analyse. If the ethical rules express the physicians' obligations in legal terms, it perfectly determines the spirit which must drive every physician thus revealing his sense of responsibility. This concept of the medical responsibility distinguishes and differentiates itself from the penalty responsibility and from the compensation responsibility which only takes place in the context of the compensation for a harm caused. The acquisition of the prime sense of the responsibility is a product of a background dominated by the experience, the example, the conscience. The expression of the medical responsibility is most of all personal, but more and more fits in with the public health issues and becomes a collective responsibility. Finally in order to meet the more and more accurate specialists' demands, the physician's responsibility which must remain within the boundaries of his competence must be fulfilled in the frame of a team. This dimension imposes on him new regulations that affect the quality of the relationship between the various contributors. An evolution of the responsibility thus grows according to the progress and within the adapted scope of ethics.     

Development of orientation preference maps in area 18 of kitten visual cortex

We investigated the development of orientation preference maps in the visual cortex of kittens by repeated optical imaging from the same animal. Orientation maps became detectable for the first time around postnatal day (P) 17 and improved continuously in strength unitl P30, the time at which their appearance became adultlike. During this developmental period the overall geometry of the maps remained unchanged, suggesting that the layout of the orientation map is specified prior to P17. Hence, before the visual cortex becomes susceptible to experience-dependent modifications its functional architecture is largely specified. This suggests that the initial development and layout of orientation preference maps are determined by intrinsic processes that are independent of visual experience. This conclusion is further supported by the result that orientation maps were well expressed at P24 in binocularly deprived kittens. Because the appearance of the first orientation-selective neurons and the subsequent development of orientation preference maps correlated well with the time course of the expression and refinement of clustered horizontal connections, we propose that these connections might contribute to the specification of orientation preference maps.     

Responsiveness of neurons in the posterior inferotemporal cortex to visual patterns in the macaque monkey

Using anesthetized and immobilized monkeys, responses of neurons in the posterior inferotemporal cortex to visual patterns were examined. Response properties were compared between the sulcus and the gyrus, extending between the anterior tip of the posterior middle temporal sulcus and the inferior occipital sulcus. Of 682 neurons tested, 37% in the sulcus (134/365) and 36% in the gyrus (113/317) responded to one or more patterns. The preference of neurons for patterns varied from neuron to neuron; some neurons responded selectively to one particular pattern, whereas others responded to two or more patterns. To evaluate response properties of neurons, two indices were calculated (the pattern preference index and the pattern selectivity index). The distributions of these indices in the sulcus did not differ significantly from those of the gyrus. Furthermore, the relationship between the pattern preference index and the pattern selectivity index for each neuron was almost the same in these two portions; most neurons responding to a small number of patterns showed inhibitory or weak responses to the worst pattern. In both portions, most neurons had receptive fields with small eccentricities and receptive field sizes were almost the same. These results suggest that the cortex in the sulcus in the posterior inferotemporal cortex is involved in the detection of features of visual patterns, similarly to the cortex in the gyrus.